Cetirizine and Levocetirizine Withdrawal Pruritus: What Pharmacists Need to Know About the FDA’s New Safety Warning

Why It Matters

The warning highlights a previously undocumented safety risk for two of the most widely used OTC allergy drugs, prompting changes in patient counseling and pharmacovigilance practices.

Key Takeaways

• FDA adds withdrawal pruritus warning to cetirizine/levocetirizine labels
• Over 200 FAERS reports link discontinuation to severe itching
• Reaction appears limited to piperazine antihistamines, not class‑wide
• Tapering or switching antihistamines mitigates withdrawal symptoms
• Pharmacists must counsel patients and report events via MedWatch

Pulse Analysis

The FDA’s decision to append a withdrawal‑pruritus warning to cetirizine and levocetirizine labels reflects growing pharmacovigilance data that challenges the long‑standing perception of these agents as benign. With over 62 million OTC packages sold annually and millions of prescriptions, the potential for a severe, abrupt itching episode after discontinuation represents a public‑health concern that could affect a sizable patient cohort. By formalizing the risk, regulators aim to improve transparency and empower clinicians to anticipate and manage this adverse effect.

Clinical investigations suggest the phenomenon is unique to the piperazine derivatives cetirizine and its R‑enantiomer levocetirizine, distinguishing them from piperidine‑based antihistamines such as loratadine and fexofenadine. The underlying mechanism remains speculative, with hypotheses ranging from histamine rebound to immune modulation. Nevertheless, case series and post‑marketing reports consistently document a temporal relationship: patients on chronic daily therapy develop intense pruritus within days of abrupt cessation, often without prior itching history. This pattern underscores the need for targeted research to elucidate pathophysiology and quantify incidence.

For pharmacy professionals, the new label mandates a proactive counseling approach. Advising patients to taper rather than stop suddenly, monitoring for emergent itching, and offering alternatives—whether a different antihistamine or adjunctive therapies like corticosteroids—can mitigate severity. Moreover, diligent adverse‑event reporting via MedWatch will enrich the FDA’s data pool, facilitating more precise risk estimates. As the market continues to expand with online sales, pharmacists serve as a critical checkpoint, ensuring safe discontinuation practices and reinforcing the broader pharmacovigilance ecosystem.

Cetirizine and Levocetirizine Withdrawal Pruritus: What Pharmacists Need to Know About the FDA’s New Safety Warning

Authors: Michelle Kaplun, PharmD Candidate; Thomas Turco, PharmD · February 19 2026

Key Takeaways

• The FDA plans label updates for cetirizine/levocetirizine due to post‑discontinuation severe itching signals, predominantly linked to cetirizine in > 200 FAERS reports.

• Onset typically occurs within days of stopping after months‑to‑years of daily use, often in patients without baseline pruritus and sometimes requiring clinical intervention.

• Evidence suggests the phenomenon is not class‑wide among second‑generation antihistamines, appearing mainly in the piperazine derivatives cetirizine and levocetirizine.

• Mitigation approaches include tapering, rechallenge, switching antihistamines, adjunct corticosteroids, and occasional off‑label biologics (dupilumab or omalizumab) for refractory cases.

• Pharmacist counseling should emphasize symptom vigilance after discontinuation, prompt referral for severe pruritus, and robust adverse‑event reporting via MedWatch to improve pharmacovigilance.

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FDA Drug Safety Communication: What Pharmacists Need to Know

In May 2025, the FDA posted a drug safety communication about the OTC and prescription allergy medications cetirizine and levocetirizine. The communication explained that a rare but serious reaction of severe itching can occur upon discontinuation of these two agents. The FDA identified over 200 cases from the FDA Adverse Event Report System (FAERS), the majority associated with cetirizine discontinuation (see Table 1). The pruritus was not present before medication use, could be serious (requiring medical intervention), and tended to appear in chronic (months‑to‑years), daily users.

Based on the evidence gathered by the FDA, there appears to be a temporal relationship between discontinuation of levocetirizine or cetirizine and pruritus. The mechanism is currently unknown. To increase patient safety, the FDA will add warnings about this possible reaction to the drugs’ prescribing information and request that manufacturers update their OTC drug‑facts labels accordingly.

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Cetirizine and Levocetirizine Usage Statistics: How Widely Are These Antihistamines Used?

Levocetirizine and cetirizine are perhaps the most widely used treatments for allergic diseases and off‑label indications. As of 2022, the FDA estimates that in the US 62.7 million OTC packages have been sold and 26.8 million prescriptions have been dispensed. With the increasing availability of online medications, the true number of patients taking these two antihistamines is likely under‑reported.

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Pharmacology of Cetirizine and Levocetirizine

Both drugs are second‑generation antihistamines that competitively inhibit histamine at H₁ receptors, reducing symptoms such as rhinitis and pruritus. Among second‑generation antihistamines, these two piperazine derivatives are related to meclizine and hydroxyzine but are unrelated to loratadine and fexofenadine, which are piperidine derivatives. Structurally, levocetirizine is the R‑enantiomer of the racemic mixture cetirizine.

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Clinical Evidence for Withdrawal Pruritus After Cetirizine or Levocetirizine Discontinuation

The current prescribing information for levocetirizine and cetirizine does not mention the possibility of pruritus after discontinuation. Pharmacovigilance data were not readily available through manufacturers or a literature review. A PubMed search using the terms “cetirizine,” “pruritis,” and “discontinuation” identified five relevant publications supporting the probability of a withdrawal reaction (see Table 2). Most evidence points to a causative relationship between discontinuation of these agents and withdrawal pruritus. The median onset is a few days after stopping, typically in chronic, daily users for months‑to‑years. The majority of reported cases were submitted by consumers and were predominantly female. Available data suggest the effect is limited to cetirizine and levocetirizine and does not appear to be class‑wide among second‑generation antihistamines.

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How Should Pharmacists Manage and Counsel Patients on Antihistamine Discontinuation Pruritus?

Pharmacists can use their expertise to help patients and health‑care providers mitigate this rare but potentially serious adverse effect.

1. Counseling – Inform patients using cetirizine or levocetirizine that a withdrawal‑related pruritus may occur after stopping the medication, especially after long‑term daily use. Advise them to monitor for new or worsening itching after discontinuation and to seek medical attention if severe.

2. Reporting – Encourage reporting of any suspected reactions to MedWatch or another appropriate adverse‑event reporting system, even if causality is uncertain.

3. Management Strategies –

   • Gradual taper of the antihistamine rather than abrupt cessation.

   • Rechallenge or restart the same agent if symptoms appear.

   • Switch to an alternative second‑generation antihistamine (e.g., loratadine, fexofenadine).

   • Adjunct corticosteroids for severe inflammation.

   • Off‑label biologics (dupilumab or omalizumab) have been used in refractory cases.

Pharmacists should also advise prescribers on these strategies and facilitate referrals for patients with severe or persistent pruritus.

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Clinical Takeaways for Pharmacists

• The FDA’s safety concern describes the reaction after discontinuation of levocetirizine and cetirizine as rare but possibly severe.

• A warning will be added to the prescribing information and OTC drug‑facts labels, although at the time of this publication no label changes were yet observable.

• The true incidence is unknown; post‑marketing pharmacovigilance data are limited, and no precise risk percentage can be reported.

• The mechanism is primarily unknown; a histamine rebound effect is one hypothesized explanation.

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References

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2. Zablotsky B, Black LI, Akinbami LJ. Diagnosed allergic conditions in children aged 0‑17 years: United States, 2021. NCHS Data Brief. 2023(459):1‑8.

3. Gutowska‑Slesik J, et al. The increase in allergic conditions based on a review of literature. Postepy Dermatol Alergol. 2023;40(1):1‑7. doi:10.5114/ada.2022.119009

4. Michelson KA, et al. Trends in emergency care for anaphylaxis. J Allergy Clin Immunol Pract. 2020;8(2):767‑768.e2. doi:10.1016/j.jaip.2019.07.018

5. FDA. “FDA requires warning about rare severe itching after stopping long‑term use of oral allergy medicines cetirizine or levocetirizine (Zyrtec, Xyzal, and other trade names).” May 16 2025. Accessed Feb 18 2026. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warning-about-rare-severe-itching-after-stopping-long-term-use-oral-allergy-medicines

6. Scolaro KL. Colds and allergy. In: Krinsky DL, et al., eds. Handbook of Nonprescription Drugs: An Interactive Approach to Self‑Care. 20th ed. APhA; 2021:530‑531.

7. Zyrtec [prescribing information]. Kenvue; 2002. Accessed Feb 18 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19835s15,%2020346s8lbl.pdf

8. Xyzal [prescribing information]. UCB, Inc; 2008. Accessed Feb 18 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022064s009lbl.pdf

9. Konkel K, Lee JY, Jones SC, et al. New onset pruritus following discontinuation of cetirizine or levocetirizine. J Allergy Clin Immunol Pract. 2025;S2213‑2198(25)01157‑2. doi:10.1016/j.jaip.2025.11.040

10. Chung AH, La Grenade L, Harinstein LM. Pruritus after discontinuation of cetirizine. Ther Adv Drug Saf. 2019;10:2042098619859996. doi:10.1177/2042098619859996

11. In brief: pruritus following antihistamine discontinuation. Scilit. 2025;67(1735):135.

12. Ekhart C, van der Horst P, van Hunsel F. Unbearable pruritus after withdrawal of (levo)cetirizine. Drug Saf Case Rep. 2016;3(1):16. doi:10.1007/s40800-016-0041-9

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